The Effect of Taurine on Diastolic Function of the Left Ventricular Myocardium in Patients with Ischemic Heart Disease Complicated by Chronic Heart Failure

The investigation is dedicated to the study of the effect of taurine on the diastolic function of the left ventricular myocardium in patients with ischemic heart disease complicated by chronic heart failure with preserved ejection fraction. The work includes a literature review, a clinical study of patients, and an analysis of the results of taurine administration at a dose of 750 mg per day over a period of 12 months. The clinical course of the disease, medium-term prognosis, dynamics of systolic and diastolic myocardial function, elastic and contractile properties of arteries, and the levels of biomarkers — NT-proBNP and galectin-3 — are studied.

The scientific novelty of the work lies in the first-time demonstrated reliable reduction in the functional class of CHF and the number of repeated hospitalizations against the background of taurine therapy, as well as the improvement of diastolic function of the left ventricular myocardium and the reduction of the stiffness of the arterial vessel wall in this category of patients.

Introduction.

Relevance of the Problem. At the present time, diseases of the cardiovascular system are the leading cause of death in economically developed countries. According to a group of researchers from Oxford who analyzed total mortality (4.1 million people) in 52 European countries in 2014, three out of every ten deaths of Europeans under the age of 65 were caused by cardiovascular pathology, reaching 37% of total mortality at the age of up to 75 years [165].

Chronic heart failure complicates the course of many cardiovascular diseases, with an increase in the number of patients being observed, while high mortality, disability, and social maladaptation of patients are preserved [185, 196]. At present, 15 million people live with heart failure in Europe, 6 million in the United States, and approximately 8 million in the Russian Federation [3, 95, 175]. At the beginning of the twenty-first century, 17.45% of hospitalized patients with heart failure died within one year of observation, and more than 50% within five years, although a trend toward reduced mortality has been noted [168, 175]. No less a complex problem for medicine is the issue of decompensation of chronic heart failure, requiring hospitalization of patients, accompanied by hospital mortality of up to 10%. Within one year, 30% of patients are again referred to inpatient care with worsening of the functional class of heart failure [14, 123, 170]. In turn, the treatment of such patients requires significant financial expenditures (26–39 million euros per 100 million population in Europe), constituting 1–3% of total healthcare expenditures in North America, Western Europe, and Latin America and 6% in the Russian Federation [111, 118].

At the present time, the basic principles of pharmacological treatment of chronic heart failure have been established, which presuppose normalization of intra-cardiac and central hemodynamics, microcirculation, activity of neurohumoral systems of the body, prevention and treatment of cardiac rhythm disturbances, sudden cardiac death, and thromboembolic syndrome [56, 155]. The principles of treatment of CHF with reduced ejection fraction have been most fully developed, while in preserved ejection fraction, the search continues for new medicinal preparations that improve patients' quality of life and are capable of reducing the frequency of repeated hospitalizations and improving the prognosis of the disease [13, 104]. One of these directions is the use of preparations with a positive effect on cellular metabolism [41, 76, 94]. One such medicinal agent is taurine, whose clinical effectiveness has been demonstrated in patients with severe chronic heart failure [62, 68, 71, 194], digitalis intoxication, and various cardiac rhythm disturbances [31, 42]. At the same time, there are isolated works on the effectiveness of the drug in patients with CHF with preserved ejection fraction [70], the influence of taurine on the stiffness of resistive vessels, diastolic function of the left ventricular myocardium, and the level of biomarkers reflecting the effectiveness of treatment and the prognosis of the disease [72, 83], which makes the proposed topic relevant.

Goal of the Investigation. To evaluate the effectiveness of taurine in the treatment of the diastolic form of CHF in patients with coronary artery disease, the dynamics of the state of diastolic function of the left ventricle, and the possibility of preventing the progression of myocardial fibrosis.

Tasks of the Investigation:

1) To study the influence of taurine on the clinical course of CHF in patients with coronary artery disease;

2) To study the influence of taurine on the medium-term prognosis of CHF in patients with coronary artery disease;

3) To study the dynamics of systolic and diastolic function of the left ventricular myocardium during taurine therapy;

4) To study the dynamics of CT-proBNP and galectin-3 concentrations during taurine therapy;

5) To study the dynamics of resistive vessel stiffness during taurine therapy.

Scientific Novelty. For the first time, it has been demonstrated that against the background of taurine therapy at a dose of 750 mg per day over a period of 12 months in patients with chronic heart failure with preserved ejection fraction and II–III functional class (according to NYHA) caused by coronary artery disease, a reliable reduction in the functional class of CHF and the number of repeated hospitalizations is observed. It has been established that the use of taurine does not affect one-year mortality but reliably improves diastolic function of the left ventricular myocardium and reduces the stiffness of the arterial vessel wall in this category of patients. For the first time, it has been shown that against the background of taurine therapy, the content of NT-proBNP and the concentration of galectin-3 in the blood reliably decrease, which testifies to a slowdown in the process of pathological remodeling of the left ventricular myocardium.

Practical Significance of the Work. The data obtained in the work make it possible to recommend the use of taurine at a dose of 750 mg per day in patients with chronic heart failure with preserved ejection fraction of II and III functional class NYHA due to coronary artery disease, in order to reduce the frequency of repeated hospitalizations within one year, improve diastolic function of the left ventricle, reduce the stiffness of resistive vessels, and the progression of myocardial fibrosis.

Implementation of the Results of the Work in Practice. The main provisions of the dissertation work have been introduced and are used in the work of departments 2, 6, 8, and 20 of the cardiology departments of City Clinical Hospital No. 15 named after O.M. Filatov, Moscow, the consultative-diagnostic center at City Clinical Hospital No. 15 named after O.M. Filatov, as well as in the educational process at the department of hospital therapy No. 1 of the clinical faculty of the Federal State Budgetary Educational Institution of Higher Education "Pirogov Russian National Research Medical University" of the Ministry of Health of Russia.